Studies are designed to test the hypothesis that hypertension of thoracic aortic coarctation, as a model of "total renal underperfusion", is renin-mediated in both acute and chronic phases and initiated by impaired perfusion of the entire renal mass. The postulated pathogenetic sequence involves initial rise in renin activity and thus blood pressure with subsequent renin-dependent compensatory volume expansion, the latter sustaining hypertension while permitting renal perfusion and thus renin activity to normalize. While indices of either renin or volume may be "normal" depending on sodium intake, the renin:volume relationship should be consistently abnormal. In inbred dogs with neonatally-induced thoracic aortic coarctation and in sham-operated, age-matched controls, we will serially examine blood pressure and indices of renin, body fluid volumes, and renal perfusion during developing, established, and post-correction phases of coarctation hypertension. Spontaneous changes with time and responses to dietary salt manipulation during each phase will be assessed using the following determinations: 1) indirect forelimb and hindlimb blood pressure; 2) Na24 volume of distribution; 3) radioiodinated serum albumin volume of distribution; 4) plasma renin activity, renin reactivity (an index of circulating modifiers of the renin reaction rate), plasma renin concentration, and renin-substrate concentration, all by radioimmunoassay of angiotensin I; 5) renal clearance of inulin and paraaminohippurate; 6) blood pressure response to angiotensin II blockage by the antagonist (Sar1, Ala8) angiotensin II. Studies are further designed to clarify the physiologic significance of the in vitro acceleration of the renin reaction measured as increased renin reactivity, observed in a variety of hypertensive states including coarctation hypertension. Finally, since the renal pressor system and renal mass are intact in the neonatal coarctation model, results will provide information on the basic physiology of the renin-angiotensin system in the unanesthetized animal. Confirmation of the hypothesis will mandate revision of current criteria for diagnosing renin-mediated mechanisms in hypertensive patients.